Prioritizing and modelling of putative drug target proteins of Candida albicans by system biology approach

Abstract

Candida albicans (C. albicans) is one of the major source of nosocomial infections in human which may prove fatal in 30% of cases. The hospital acquired infection is very difficult to affectively treat due to the presence of drug resistant pathogenic strains, therefore there is a need to find alternative drug targets to cure this infection. In silico and computational level frame work was used to prioritize and establish antifungal drug targets of Candida albicans. The identification of putative drug targets was based on acquiring completely 5090 annotated genes of Candida albicans from available databases which was categorized into essential and non-essential genes. The result indicated 9% proteins were essential that could become potential candidates for intervention which might result in pathogen death. We studied cluster of orthologs and the subtractive genomic analysis of these essential proteins against human genome as a reference to minimize the side effects. It was seen that 14% of Candidal proteins were evolutionary related to the human proteins while 86% are non-human homologs. In next step for the selection of compatible drug targets, the non-human homologs were sequentially compared to human microbiome data to minimize the potential effects against gut flora which accumulated to 38% of essential genome. The sub-cellular localization of these candidate proteins in fungal cellular systems exhibited that 80% are cytoplasmic, 10% are mitochondrial and remaining 10 % are associated with cell wall. The role of these non-human and non-gut flora putative target proteins in Candidal biological pathways was studied and on the basis of their integrated and critical role 4-proteins were selected for molecular modeling.  For drug designing and development, five quality and reliable protein models with more than 70% homology were constructed. Our study will be an effective framework for drug target identifications of pathogenic microbial strains and development of new therapies against these infections.